tbuckley/cabot-search huggingface dataset:
Incidence of Cardiovascular Events in Patients Treated With Immune Checkpoint Inhibitors
Authors: Dorien Laenens, Yuling Yu, Béatrice Santens, Johanna Jacobs, Benoit Beuselinck, Oliver Bechter, Els Wauters, Jan Staessen, Stefan Janssens, Lucas Van Aelst
Journal: Journal of Clinical Oncology (2022)

In rare cases, immune checkpoint inhibitors (ICIs) cause immune-mediated myocarditis. However, true incidence of other major adverse cardiovascular events (MACEs) after ICI treatment remains unknown, mainly because late occurring side effects are rarely reported in prospective clinical trials. The aims of this study were (1) to identify incidence and risk factors of MACE in a real-life ICI-treated cancer cohort and (2) to compare incidence rates with patients with cancer who are not treated with ICIs and population controls.In total, 672 patients treated with ICIs were included. The primary end point was MACE, a composite of acute coronary syndrome, heart failure (HF), stroke, and transient ischemic attack. Secondary outcomes were acute coronary syndrome and HF separately. Incidence rates were compared between groups after matching according to age, sex, cardiovascular history, and cancer type.The incidence of MACE was 10.3% during a median follow-up of 13 (interquartile range, 6-22) months. In multivariable analysis, a history of HF (hazard ratio 2.27; 95% CI, 1.03 to 5.04; P = .043) and valvular heart disease (hazard ratio 3.01; 95% CI, 1.05 to 8.66; P = .041) remained significantly associated with MACE. Cumulative incidence rates were significantly higher in the ICI group compared with the cancer cohort not exposed to ICI and the population controls, mainly driven by a higher risk of HF events.Cardiovascular events during and after ICI treatment are more common than currently appreciated. Patients at risk are those with a history of cardiovascular disease. Compared with matched cancer and population controls, MACE incidence rates are significantly higher, suggesting a potential harmful effect of ICI treatment besides the underlying risk.
Evaluating the amount of knowledge about palliative care concepts among health professionals and medical students in the Gaza Strip: a cross-sectional study
Authors: Abdallah Alwali, Ahmad Alborno, Amal Shaikhah, Esraa AbuHamed, Shrooq Abulqumboz, Ayah AbuQamar, Abedelrahman Diab, Bettina Bottcher
Journal: The Lancet (2022)
Renal Deletion of LRRC8/VRAC Channels Induces Proximal Tubulopathy
Authors: Karen I. López-Cayuqueo, Rosa Planells-Cases, Matthias Pietzke, Anna Oliveras, Stefan Kempa, Sebastian Bachmann, Thomas J. Jentsch
Journal: Journal of the American Society of Nephrology (2022)

Volume-regulated anion channels (VRACs) are heterohexamers of LRRC8A with LRRC8B, -C, -D, or -E in various combinations. Depending on the subunit composition, these swelling-activated channels conduct chloride, amino acids, organic osmolytes, and drugs. Despite VRACs' role in cell volume regulation, and large osmolarity changes in the kidney, neither the localization nor the function of VRACs in the kidney is known.Mice expressing epitope-tagged LRRC8 subunits were used to determine the renal localization of all VRAC subunits. Mice carrying constitutive deletions of Lrrc8b-e, or with inducible or cell-specific ablation of Lrrc8a, were analyzed to assess renal functions of VRACs. Analysis included histology, urine and serum parameters in different diuresis states, and metabolomics.The kidney expresses all five VRAC subunits with strikingly distinct localization. Whereas LRRC8C is exclusively found in vascular endothelium, all other subunits are found in the nephron. LRRC8E is specific for intercalated cells, whereas LRRC8A, LRRC8B, and LRRC8D are prominent in basolateral membranes of proximal tubules. Conditional deletion of LRRC8A in proximal but not distal tubules and constitutive deletion of LRRC8D cause proximal tubular injury, increased diuresis, and mild Fanconi-like symptoms.VRAC/LRRC8 channels are crucial for the function and integrity of proximal tubules, but not for more distal nephron segments despite their larger need for volume regulation. LRRC8A/D channels may be required for the basolateral exit of many organic compounds, including cellular metabolites, in proximal tubules. Proximal tubular injury likely results from combined accumulation of several transported molecules in the absence of VRAC channels.
Quantitative microbial risk assessment to estimate annual infection risk and disease burden attributable to Escherichia coli O157:H7 in drinking water in the Gaza Strip: a prospective study
Authors: Samer Abuzerr, Mahdi Hadi, Kate Zinszer, Simin Nasseri, Masud Yunesian, Amir Hossein Mahvi, Ramin Nabizadeh
Journal: The Lancet (2022)
PB1968: EPIGENETIC AND GENETIC INVESTIGATION OF SOCS-1 GENE IN PATIENTS WITH MULTIPLE MYELOMA
Authors: I. Serin, F. C. TUNCEL, S. PEHLIVAN, Y. OYACI, M. PEHLIVAN
Journal: HemaSphere (2022)

Background: The suppressor of cytokine signaling-1 (SOCS-1) functions to induce an appropriate immune response and is an essential physiological regulator of interferon signaling. DNA methylation, an epigenetic regulatory mechanism studied in multiple myeloma (MM) and many tumors, involves the addition of a methyl group to the carbon 5 position of cytosine. Aims: In this study, besides comparing SOCS-1 gene hypermethylation between patients with MM and healthy controls, it was aimed to demonstrate the effect of SOCS-1 gene distribution and additionally, the effect of hypermethylation of SOCS-1 on progression free survival (PFS) and overall survival (OS). Methods: In this study, 120 patients diagnosed with MM between January 2018 and 2020 and 80 healthy individuals were included. The distribution of the SOCS-1 genotypes was statistically compared between patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined. Results: CA/CA genotype of SOCS-1 was found to be statistically significantly higher in healthy controls (p=0,001), while Del/Del genotype was significantly higher in patients with MM (p=0,034). The percent methylated reference (PMR) value of the SOCS-1 gene was found to be significantly higher in the healthy controls (median: 43,48, range: 2,76-247,75; p=0,001). The SOCS-1 genotype distribution had no effect on PFS and OS (for PFS, p=0,229; for OS, p=0,763). Patients with a PMR value of <43,48 had a significantly longer PFS (for <43,48 %56, for ≥43,48 %43; p=0,027). Image:Summary/Conclusion: The PMR value of the SOCS-1 gene was found to be significantly higher in the healthy control group. Patients with a PMR value of <43,48 were found to have a significantly longer PFS. The effects of SOCS-1 polymorphisms on the pathogenesis of MM and SOCS-1 methylation will shed light on the literature.
Updated U.S. Public Health Service Guideline for Testing of Transplant Candidates Aged &lt;12 Years for Infection with HIV, Hepatitis B Virus, and Hepatitis C Virus — United States, 2022
Authors: Rebecca J. Free, Marilyn E. Levi, James S. Bowman, Danae Bixler, John T. Brooks, Kate Buchacz, Anne Moorman, James Berger, Sridhar V. Basavaraju
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The U.S. Public Health Service (PHS) has periodically published recommendations about reducing the risk for transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) through solid organ transplantation (1-4). Updated guidance published in 2020 included the recommendation that all transplant candidates receive HIV, HBV, and HCV testing during hospital admission for transplant surgery to more accurately assess their pretransplant infection status and to better identify donor transmitted infection (4). In 2021, CDC was notified that this recommendation might be unnecessary for pediatric organ transplant candidates because of the low likelihood of infection after the perinatal period and out of concern that the volume of blood drawn for testing could negatively affect critically ill children.* CDC and other partners reviewed surveillance data from CDC on estimates of HIV, HBV, and HCV infection rates in the United States and data from the Organ Procurement & Transplantation Network (OPTN)† on age and weight distributions among U.S. transplant recipients. Feedback from the transplant community was also solicited to understand the impact of changes to the existing policy on organ transplantation. The 2020 PHS guideline was accordingly updated to specify that solid organ transplant candidates aged <12 years at the time of transplantation who have received postnatal infectious disease testing are exempt from the recommendation for HIV, HBV, and HCV testing during hospital admission for transplantation.
The Role of Perfusion Computed Tomography as a Predictor of Pancreatic Necrosis in Acute Pancreatitis
Authors: I. V. Bazhukhina, N. V. Klimova, A. A. Gaus, N. N. Petrova
Journal: Radiology - Practice (2022)

The article analyzes the data obtained as a result of the use of imaging methods in 35 patients with a new coronavirus infection who were treated in the infectious diseases department of the Surgut Regional Clinical Hospital. In the course of treatment in this group of patients, the appearance of symptoms of acute pancreatitis was noted. The criteria for inclusion in the study, in addition to the presence of a coronavirus infection confirmed by PCR, were a laboratory-detected increase in blood amylase and lipase. In the infectious diseases hospital, patients underwent perfusion computed tomography (PCT) when the first symptoms of acute pancreatitis appeared. Subsequently, in accordance with national recommendations, the entire group of patients underwent multislice computed tomography (MSCT) with bolus intravenous contrast on days 3–5. As a result of the complex of imaging research methods, 40 % (14 patients out of 35) showed a decrease in perfusion parameters characterizing the development of ischemic lesions of the pancreatic parenchyma. Later, in 11.4 % (in 4 patients out of 14), this was confirmed by MSCT with bolus intravenous contrast enhancement and was expressed as the formation of a site of destruction of the pancreatic parenchyma. In 60 % of cases (35 in 21 patients), there was no decrease in perfusion parameters during PCT, which was also later confirmed by contrast-enhanced computed tomography. Thus, we can conclude that perfusion computed tomography can play the role of an effective predictor of the development of necrotic changes in the pancreatic parenchyma in patients with acute pancreatitis that developed against the background of a new coronavirus infection.
Incidental Finding of Urinary Bladder Retention on the 99mTc-Labeled Red Blood Cells Subcutaneous Radionuclide Venography
Authors: Yi-Ling Chang, Chih-Ting Liu, Hsiu-Lan Chu, Yu-Wen Chen, Chia-Yang Lin
Journal: Clinical Nuclear Medicine (2015)

We present a case with swelling of the lower extremities, shortness of breath, and hyponatremia. (99m)Tc-labeled red blood cells subcutaneous radionuclide venography was performed to rule out deep vein thrombosis. Disturbed iliac venous flow and a photopenic lesion were noted in the lower abdomen on the planar imaging. SPECT/CT imaging revealed a hypodense lesion in the lower abdomen. Distended urinary bladder and retention were impressed. After approximately 4000 mL of urine was drained, symptoms were dramatically relieved, and improvement of hyponatremia was also observed.
The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis
Authors: Wesley T. Richerson, Brian D. Schmit, Dawn F. Wolfgram
Journal: Journal of the American Society of Nephrology (2022)

Patients with kidney failure treated with hemodialysis (HD) may be at risk for cerebral hypoperfusion due to HD-induced BP decline in the setting of impaired cerebral autoregulation. Cerebrovascular reactivity (CVR), the cerebrovascular response to vasoactive stimuli, may be a useful indicator of cerebral autoregulation in the HD population and identify those at risk for cerebral hypoperfusion. We hypothesize that CVR combined with intradialytic BP changes will be associated with declines in cerebral oxygenation saturation (ScO
Forthcoming Meetings
Journal: Neuro-Oncology (2022)

Journal Article Forthcoming Meetings Get access Neuro-Oncology, Volume 24, Issue 7, July 2022, Page 1217, https://doi.org/10.1093/neuonc/noac153 Published: 01 July 2022 Article history Published: 01 July 2022 Corrected and typeset: 07 July 2022
Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study
Authors: Carmen Piernas, Martina Patone, Nerys M Astbury, Min Gao, Aziz Sheikh, Kamlesh Khunti, Manu Shankar-Hari, Sharon Dixon, Carol Coupland, Paul Aveyard, Julia Hippisley-Cox, Susan A Jebb
Journal: The Lancet Diabetes & Endocrinology (2022)

A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England.
NHS launches first standardised induction programme for international medical graduates
Authors: Joy Hodkinson, Pat Lok
Journal: BMJ (2022)

<h3>Background</h3> Current literature suggests that anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) have comparable clinical outcomes for the treatment of cervical radiculopathy. Given similar outcomes, an understanding of differences in long-term societal costs can help guide resource utilization. The purpose of this study was to compare the relative long-term societal costs of anterior cervical discectomy and fusion (ACDF) to cervical disc arthroplasty (CDA) for the treatment of single level cervical disc disease by considering upfront surgical costs, lost productivity, and risk of subsequent revision surgery. <h3>Methods</h3> We completed an economic and decision analysis using a Markov model to evaluate the long-term societal costs of ACDF and CDA in a theoretical cohort of 45-65 year old patients with single level cervical disc disease who have failed nonoperative treatment. <h3>Results</h3> The long-term societal costs for a 45-year old patient undergoing ACDF are $31,178 while long-term costs for CDA are $24,119. Long-term costs for CDA remain less expensive throughout the modeled age range of 45 to 65 years old. Sensitivity analysis demonstrated that CDA remains less expensive than ACDF as long as annual reoperation rate remains below 10.5% annually. <h3>Conclusions</h3> Based on current data, CDA has lower long-term societal costs than ACDF for patients 45-65 years old by a substantial margin. Given reported reoperation rates of 2.5% for CDA, it is the preferred treatment for cervical radiculopathy from an economic perspective.
Carcinogenicity of occupational exposure as a firefighter
Authors: Paul A Demers, David M DeMarini, Kenneth W Fent, Deborah C Glass, Johnni Hansen, Olorunfemi Adetona, Maria HG Andersen, Laura E Beane Freeman, Alberto J Caban-Martinez, Robert D Daniels, Timothy R Driscoll, Jaclyn M Goodrich, Judith M Graber, Tracy L Kirkham, Kristina Kjaerheim, David Kriebel, Alexandra S Long, Luana C Main, Marta Oliveira, Susan Peters, Lauren R Teras, Emily R Watkins, Jefferey L Burgess, Anna A Stec, Paul A White, Nathan L DeBono, Lamia Benbrahim-Tallaa, Aline de Conti, Fatiha El Ghissassi, Yann Grosse, Leslie T Stayner, Eero Suonio, Susana Viegas, Roland Wedekind, Pauline Boucheron, Bayan Hosseini, Joanne Kim, Hana Zahed, Heidi Mattock, Federica Madia, Mary K Schubauer-Berigan
Journal: The Lancet Oncology (2022)
Clinical Utility of Cardiovascular Risk Scores for Identification of People With Type 2 Diabetes More Likely to Benefit From Either GLP-1 Receptor Agonist or SGLT2 Inhibitor Therapy
Authors: Julian W. Sacre, Dianna J. Magliano, Jonathan E. Shaw
Journal: Diabetes Care (2022)

Differentiation of risk for major adverse cardiovascular events (MACE) from heart failure hospitalization (HHF) or kidney disease is important when selecting glucose-lowering therapy. We investigated the ability of separate MACE and HHF risk scores to 1) differentiate MACE from HHF risk; and 2) identify individuals more likely to benefit from either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2is).We identified three trials in type 2 diabetes that reported cardiovascular outcomes stratified by Thrombolysis In Myocardial Infarction Risk Scores for MACE and HHF. Pooled placebo-arm rates of HHF, MACE, and their ratio and estimated GLP-1RA- and SGLT2i-mediated reductions in events (MACE and HHF combined) were compared across cardiovascular risk strata in the trial populations.The HHF rate was less frequent than MACE at all risk levels but increased from 18% of the MACE rate at low-intermediate HHF risk to 61% at highest HHF risk. Similarly, with increasing MACE risk, the incidence of HHF increased from 19% of the MACE incidence in those at low MACE risk to 51% in those with the highest MACE risk. Estimated GLP-1RA- and SGLT2i-mediated reductions in cardiovascular events were similar in those at low-intermediate MACE or HHF risk but tended to favor SGLT2is at higher risk levels of both scores.A greater increase in the rate of HHF relative to MACE was observed with progressively higher cardiovascular risk, regardless of the risk score applied. Consequently, SGLT2is may offer greater overall cardiovascular protection in those at highest MACE risk, not just those at highest HHF risk.
Caspase-3–Induced Activation of SREBP2 Drives Drug Resistance via Promotion of Cholesterol Biosynthesis in Hepatocellular Carcinoma
Authors: Etienne Ho Kit Mok, Carmen Oi Ning Leung, Lei Zhou, Martina Mang Leng Lei, Hoi Wing Leung, Man Tong, Tin Lok Wong, Eunice Yuen Ting Lau, Irene Oi Lin Ng, Jin Ding, Jing Ping Yun, Jun Yu, Hui Lian Zhu, Chi Ho Lin, Dan Lindholm, Kit Sum Leung, Jonathan D. Cybulski, David M. Baker, Stephanie Ma, Terence Kin Wah Lee
Journal: Cancer Research (2022)

Abstract Accumulating evidence has demonstrated that drug resistance can be acquired in cancer through the repopulation of tumors by cancer stem cell (CSC) expansion. Here, we investigated mechanisms driving resistance and CSC repopulation in hepatocellular carcinoma (HCC) as a cancer model using two drug-resistant, patient-derived tumor xenografts that mimicked the development of acquired resistance to sorafenib or lenvatinib treatment observed in patients with HCC. RNA sequencing analysis revealed that cholesterol biosynthesis was most commonly enriched in the drug-resistant xenografts. Comparison of the genetic profiles of CD133+ stem cells and CD133− bulk cells from liver regeneration and HCC mouse models showed that the cholesterol pathway was preferentially upregulated in liver CSCs compared with normal liver stem cells. Consistently, SREBP2-mediated cholesterol biosynthesis was crucial for the augmentation of liver CSCs, and loss of SREBP2 conferred sensitivity to tyrosine kinase inhibitors, suggesting a role in regulation of acquired drug resistance in HCC. Similarly, exogenous cholesterol-treated HCC cells showed enhanced cancer stemness abilities and drug resistance. Mechanistically, caspase-3 (CASP3) mediated cleavage of SREBP2 from the endoplasmic reticulum to promote cholesterol biosynthesis, which consequently caused resistance to sorafenib/lenvatinib treatment by driving activation of the sonic hedgehog signaling pathway. Simvastatin, an FDA-approved cholesterol-lowering drug, not only suppressed HCC tumor growth but also sensitized HCC cells to sorafenib. These findings demonstrate that CSC populations in HCC expand via CASP3-dependent, SREBP2-mediated cholesterol biosynthesis in response to tyrosine kinase inhibitor therapy and that targeting cholesterol biosynthesis can overcome acquired drug resistance. Significance: This study finds that cholesterol biosynthesis supports the expansion of cancer stem cell populations to drive resistance to tyrosine kinase inhibitor therapy in hepatocellular carcinoma, identifying potential therapeutic approaches for improving cancer treatment.
Rehabilitation after anterior cruciate ligament and meniscal injuries: a best-evidence synthesis of systematic reviews for the OPTIKNEE consensus
Authors: Adam G Culvenor, Michael A Girdwood, Carsten B Juhl, Brooke E Patterson, Melissa J Haberfield, Pætur M Holm, Alessio Bricca, Jackie L Whittaker, Ewa M Roos, Kay M Crossley
Journal: British Journal of Sports Medicine (2022)

Objective Synthesise evidence for effectiveness of rehabilitation interventions following ACL and/or meniscal tear on symptomatic, functional, clinical, psychosocial, quality of life and reinjury outcomes. Design Overview of systematic reviews with Grading of Recommendations Assessment, Development and Evaluation certainty of evidence. Data sources MEDLINE, EMBASE, CINAHL, SPORTDiscus and Cochrane Library. Eligibility criteria Systematic reviews of randomised controlled trials investigating rehabilitation interventions following ACL and/or meniscal tears in young adults. Results We included 22 systematic reviews (142 trials of mostly men) evaluating ACL-injured individuals and none evaluating isolated meniscal injuries. We synthesised data from 16 reviews evaluating 12 different interventions. Moderate-certainty evidence was observed for: (1) neuromuscular electrical stimulation to improve quadriceps strength; (2) open versus closed kinetic chain exercises to be similarly effective for quadriceps strength and self-reported function; (3) structured home-based versus structured in-person rehabilitation to be similarly effective for quadriceps and hamstring strength and self-reported function; and (4) postoperative knee bracing being ineffective for physical function and laxity. There was low-certainty evidence that: (1) preoperative exercise therapy improves self-reported and physical function postoperatively; (2) cryotherapy reduces pain and analgesic use; (3) psychological interventions improve anxiety/fear; and (4) whole body vibration improves quadriceps strength. There was very low-certainty evidence that: (1) protein-based supplements improve quadriceps size; (2) blood flow restriction training improves quadriceps size; (3) neuromuscular control exercises improve quadriceps and hamstring strength and self-reported function; and (4) continuous passive motion has no effect on range of motion. Conclusion The general level of evidence for rehabilitation after ACL or meniscal tear was low. Moderate-certainty evidence indicates that several rehabilitation types can improve quadriceps strength, while brace use has no effect on knee function/laxity.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Currently, there is no approved targeted therapy option for treatment na€ ve patients with AML harboring a FLT3 mutation ineligible for intensive therapy.Konopleva and colleagues investigated the efficacy of venetoclax plus azacitidine in an FLT3mutated AML population and reported that the remission rates and OS among patients with or without FLT3 mutation were similar, suggesting that venetoclax and azacitidine maybe be used for treatment na€ ve AML patients who are ineligible for intensive chemotherapy regimens irrespective of FLT3 mutations.They also observed higher remission rates among patients exhibiting both FLT3-ITD and TKD mutations; however, the impact on OS warrants further investigation.